NO845277L

NO845277L - Fremgangsmaate til fremstilling av nye optisk aktive penemforbindelser.

Fremgangsmaate til fremstilling av nye optisk aktive penemforbindelser.

Info

Publication number: NO845277L
Authority: NO; Norway
Prior art keywords: lower alkyl; formula; amino; penem; substituted
Prior art date: 1983-12-30

Application number

NO845277A

Other languages

English (en)

Norwegian (no)

Inventor

Marc Lang

Original Assignee

Ciba Geigy Ag

Priority date

1983-12-30

Filing date

1984-12-28

Publication date

1985-07-01

1984-12-28 Application filed by Ciba Geigy Ag filed Critical Ciba Geigy Ag

1985-07-01 Publication of NO845277L publication Critical patent/NO845277L/no

Links

238000000034 method Methods 0.000 title claims description 38
238000004519 manufacturing process Methods 0.000 title claims description 13
HHXMXAQDOUCLDN-RXMQYKEDSA-N penem Chemical compound S1C=CN2C(=O)C[C@H]21 HHXMXAQDOUCLDN-RXMQYKEDSA-N 0.000 title description 2
-1 cyano, sulfo, sulfamoyl Chemical group 0.000 claims description 377
150000001875 compounds Chemical class 0.000 claims description 218
125000000217 alkyl group Chemical group 0.000 claims description 216
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 124
150000003839 salts Chemical class 0.000 claims description 70
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 63
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 57
229910052736 halogen Inorganic materials 0.000 claims description 41
150000002367 halogens Chemical class 0.000 claims description 40
239000000203 mixture Substances 0.000 claims description 33
125000003545 alkoxy group Chemical group 0.000 claims description 25
230000003287 optical effect Effects 0.000 claims description 24
125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
230000004962 physiological condition Effects 0.000 claims description 22
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 21
125000003282 alkyl amino group Chemical group 0.000 claims description 20
150000002148 esters Chemical class 0.000 claims description 20
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 20
229910052757 nitrogen Inorganic materials 0.000 claims description 19
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 18
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
125000004043 oxo group Chemical group O=* 0.000 claims description 18
125000005236 alkanoylamino group Chemical group 0.000 claims description 16
125000004423 acyloxy group Chemical group 0.000 claims description 14
125000000524 functional group Chemical group 0.000 claims description 13
238000002360 preparation method Methods 0.000 claims description 13
125000005103 alkyl silyl group Chemical group 0.000 claims description 12
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 12
125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 10
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 10
125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
230000008569 process Effects 0.000 claims description 9
125000004414 alkyl thio group Chemical group 0.000 claims description 8
150000001768 cations Chemical class 0.000 claims description 8
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 7
125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 7
125000003118 aryl group Chemical group 0.000 claims description 7
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 7
125000002950 monocyclic group Chemical group 0.000 claims description 7
229910052698 phosphorus Inorganic materials 0.000 claims description 7
239000011574 phosphorus Substances 0.000 claims description 7
125000005237 alkyleneamino group Chemical group 0.000 claims description 6
125000005605 benzo group Chemical group 0.000 claims description 6
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
125000002217 penem group Chemical group 0.000 claims description 6
239000000825 pharmaceutical preparation Substances 0.000 claims description 6
125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims description 5
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 5
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 5
125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 claims description 5
125000003431 oxalo group Chemical group 0.000 claims description 5
125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims description 5
125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 claims description 4
150000001356 alkyl thiols Chemical class 0.000 claims description 4
150000002894 organic compounds Chemical class 0.000 claims description 4
125000003396 thiol group Chemical class [H]S* 0.000 claims description 4
SQYOOFBNLMSPNS-YLWLKBPMSA-N (5r,6s)-6-(hydroxymethyl)-3-imidazol-1-yl-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound S([C@@H]1[C@H](C(N1C=1C(O)=O)=O)CO)C=1N1C=CN=C1 SQYOOFBNLMSPNS-YLWLKBPMSA-N 0.000 claims description 3
238000007344 nucleophilic reaction Methods 0.000 claims description 3
125000000369 oxido group Chemical group [*]=O 0.000 claims description 3
CKNSWUMRDLTKTL-YLWLKBPMSA-N (5r,6s)-6-(hydroxymethyl)-7-oxo-3-pyrazol-1-yl-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound S([C@@H]1[C@H](C(N1C=1C(O)=O)=O)CO)C=1N1C=CC=N1 CKNSWUMRDLTKTL-YLWLKBPMSA-N 0.000 claims description 2
FJMFEXKXATZKGL-IMTBSYHQSA-N (5r,6s)-6-(hydroxymethyl)-7-oxo-3-pyrrol-1-yl-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound S([C@@H]1[C@H](C(N1C=1C(O)=O)=O)CO)C=1N1C=CC=C1 FJMFEXKXATZKGL-IMTBSYHQSA-N 0.000 claims description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
239000000463 material Substances 0.000 claims description 2
239000001301 oxygen Substances 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
229910052717 sulfur Inorganic materials 0.000 claims description 2
239000011593 sulfur Substances 0.000 claims description 2
JRYXDGLHVXESAK-OIBJUYFYSA-N (5r,6s)-3-(4,5-dimethylimidazol-1-yl)-6-(hydroxymethyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound CC1=C(C)N=CN1C1=C(C(O)=O)N2C(=O)[C@H](CO)[C@H]2S1 JRYXDGLHVXESAK-OIBJUYFYSA-N 0.000 claims 1
BDPQLFZFQRQZAT-IMTBSYHQSA-N (5r,6s)-6-(hydroxymethyl)-3-(4-methylimidazol-1-yl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1=NC(C)=CN1C1=C(C(O)=O)N2C(=O)[C@H](CO)[C@H]2S1 BDPQLFZFQRQZAT-IMTBSYHQSA-N 0.000 claims 1
ZIIARJBMZYEKTA-IMTBSYHQSA-N (5r,6s)-6-(hydroxymethyl)-3-(4-methylpyrazol-1-yl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1=C(C)C=NN1C1=C(C(O)=O)N2C(=O)[C@H](CO)[C@H]2S1 ZIIARJBMZYEKTA-IMTBSYHQSA-N 0.000 claims 1
DZSPPCXUGSMDRW-MHTLYPKNSA-N (5r,6s)-6-(hydroxymethyl)-7-oxo-3-(1,2,4-triazol-1-yl)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound S([C@@H]1[C@H](C(N1C=1C(O)=O)=O)CO)C=1N1C=NC=N1 DZSPPCXUGSMDRW-MHTLYPKNSA-N 0.000 claims 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 160
XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 115
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 72
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 69
235000002639 sodium chloride Nutrition 0.000 description 64
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 40
238000006243 chemical reaction Methods 0.000 description 39
239000000460 chlorine Substances 0.000 description 38
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
239000007858 starting material Substances 0.000 description 33
239000002253 acid Substances 0.000 description 31
239000000741 silica gel Substances 0.000 description 31
229910002027 silica gel Inorganic materials 0.000 description 31
239000000243 solution Substances 0.000 description 29
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
239000002585 base Substances 0.000 description 20
239000011541 reaction mixture Substances 0.000 description 19
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 18
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
125000003277 amino group Chemical group 0.000 description 16
239000003480 eluent Substances 0.000 description 16
238000004587 chromatography analysis Methods 0.000 description 15
125000006239 protecting group Chemical group 0.000 description 14
229910052783 alkali metal Inorganic materials 0.000 description 13
239000003795 chemical substances by application Substances 0.000 description 13
239000008363 phosphate buffer Substances 0.000 description 13
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
239000012442 inert solvent Substances 0.000 description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
239000012074 organic phase Substances 0.000 description 12
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
229910052938 sodium sulfate Inorganic materials 0.000 description 12
235000011152 sodium sulphate Nutrition 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
125000002252 acyl group Chemical group 0.000 description 11
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
150000001340 alkali metals Chemical class 0.000 description 10
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
230000002829 reductive effect Effects 0.000 description 10
238000003756 stirring Methods 0.000 description 10
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
PHGLYQGVAGLHTN-UHFFFAOYSA-N 2-(triphenyl-$l^{5}-phosphanylidene)acetic acid Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)O)C1=CC=CC=C1 PHGLYQGVAGLHTN-UHFFFAOYSA-N 0.000 description 9
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
229910052751 metal Inorganic materials 0.000 description 9
239000002184 metal Substances 0.000 description 9
125000001424 substituent group Chemical group 0.000 description 9
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 9
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
239000013543 active substance Substances 0.000 description 8
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 8
150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
229910052801 chlorine Inorganic materials 0.000 description 8
239000012043 crude product Substances 0.000 description 8
239000000047 product Substances 0.000 description 8
235000015424 sodium Nutrition 0.000 description 8
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
125000003638 stannyl group Chemical group [H][Sn]([H])([H])* 0.000 description 8
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 7
150000007513 acids Chemical class 0.000 description 7
150000008064 anhydrides Chemical class 0.000 description 7
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
229910052794 bromium Inorganic materials 0.000 description 7
125000001589 carboacyl group Chemical group 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
239000002904 solvent Substances 0.000 description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
229910052784 alkaline earth metal Inorganic materials 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
238000001816 cooling Methods 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
150000004820 halides Chemical class 0.000 description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
229910052763 palladium Inorganic materials 0.000 description 6
238000006722 reduction reaction Methods 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
239000011734 sodium Substances 0.000 description 6
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
239000001257 hydrogen Substances 0.000 description 5
229910052739 hydrogen Inorganic materials 0.000 description 5
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
150000003254 radicals Chemical class 0.000 description 5
238000005160 1H NMR spectroscopy Methods 0.000 description 4
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 4
XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 4
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 4
HHLFWLYXYJOTON-UHFFFAOYSA-N Glyoxylic acid Natural products OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
230000002378 acidificating effect Effects 0.000 description 4
238000006136 alcoholysis reaction Methods 0.000 description 4
OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
239000012267 brine Substances 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
150000004292 cyclic ethers Chemical class 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
238000006460 hydrolysis reaction Methods 0.000 description 4
239000011261 inert gas Substances 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
239000003921 oil Substances 0.000 description 4
238000000746 purification Methods 0.000 description 4
230000009467 reduction Effects 0.000 description 4
238000007363 ring formation reaction Methods 0.000 description 4
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 4
235000009518 sodium iodide Nutrition 0.000 description 4
159000000000 sodium salts Chemical class 0.000 description 4
GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 4
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CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
229940031000 streptococcus pneumoniae Drugs 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
OXLHSVMFGCMPNB-UHFFFAOYSA-N tert-butylsulfanylmethyl-[(4-methoxyphenyl)methyl]azanium;chloride Chemical compound [Cl-].COC1=CC=C(C[NH2+]CSC(C)(C)C)C=C1 OXLHSVMFGCMPNB-UHFFFAOYSA-N 0.000 description 1
WMXCDAVJEZZYLT-UHFFFAOYSA-N tert-butylthiol Chemical compound CC(C)(C)S WMXCDAVJEZZYLT-UHFFFAOYSA-N 0.000 description 1
150000003510 tertiary aliphatic amines Chemical class 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
QSUJAUYJBJRLKV-UHFFFAOYSA-M tetraethylazanium;fluoride Chemical compound [F-].CC[N+](CC)(CC)CC QSUJAUYJBJRLKV-UHFFFAOYSA-M 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
230000017105 transposition Effects 0.000 description 1
TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
239000005051 trimethylchlorosilane Substances 0.000 description 1
UEWNEQVNIYYFFF-UHFFFAOYSA-N triphenylphosphanium;dibromide Chemical compound [Br-].[Br-].C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 UEWNEQVNIYYFFF-UHFFFAOYSA-N 0.000 description 1
238000002211 ultraviolet spectrum Methods 0.000 description 1
SCXZATZIVUFOFT-UHFFFAOYSA-N undec-5-ene Chemical compound [CH2]CCCC=CCCCCC SCXZATZIVUFOFT-UHFFFAOYSA-N 0.000 description 1
238000005303 weighing Methods 0.000 description 1
238000012982 x-ray structure analysis Methods 0.000 description 1